Antiproliferative alkaloids from Crinum zeylanicum.

Crinum zeylanicum is used in folk medicine as a rubefacient in rheumatism, a treatment for malaria or as a poison. Complex alkaloid profiles in C. zeylanicum plant organs were revealed by GC-MS analysis, including several bioactive compounds. Crinine, lycorine, 11-O-acetoxyambelline, ambelline, 6-hydroxybuphanidrine and 6-ethoxybuphanidrine (an artefact of the isolation procedure) were isolated. Crinine, 6-hydroxybuphanidrine and 6-ethoxybuphanidrine showed antiproliferative effects against human tumor cell lines, crinine being the most active (IC₅₀ 14.04 μM against HL-60/Dox). The latter compound induced apoptosis in a dose-dependent manner in HL-60 and MDA-MB-231 cell lines. Structure-activity relationships in the studied molecules indicated that the hydrogenation of the double bond at C1-C2 leads to a loss of activity, whereas substitutions at C6, C8 and C11 affect their cytotoxicity.